page_title: Gluten immunochemistry
section_title: HLA-DQ recognition of gluten
hierarchical_section_title: Gluten immunochemistry / HLA-DQ recognition of gluten
caption_attribution_description: English: Image shows how DQ2.5 (trans) can be formed from the haplotype DQ2.2/DQ7.5 phenotype. The circled DQ isoform (receptor) is DQ2.5 trans. DQB1*0202 bearing molecules have a change outside the binding cleft that make it identical in function to DQB1*0201 of DQA1*0501:DQB1*0201 phenotype.
context_page_description: The immunochemistry of Triticeae glutens is important in several inflammatory diseases. It can be subdivided into innate responses, class II mediated presentation, class I meditiated stimulation of killer cells, and antibody recognition. The responses to gluten proteins and polypeptide regions differs according to the type of gluten sensitivity. The response is also dependent on the genetic makeup of the human leukocyte antigen genes. In gluten sensitive enteropathy, there are 4 types of recognition, innate immunity, HLA-DQ, and antibody recognition of gliadin and transglutaminase. With idiopathic gluten sensitivity only antibody recognition to gliadin has been resolved. In wheat allergy, the response pathways are mediated through IgE against other wheat proteins and other forms of gliadin.
context_section_description: HLA-DQ proteins present polypeptide regions of proteins of about 9 amino acids and larger in size (10 to 14 residues in involved in binding is common for gliadin) to T lymphocytes.
  Gliadin proteins can be adsorbed by APC. After digestion in the lysozomes of APCs, glaidin peptides can be recycled to the cell's surface bound to DQ, or they can be bound and presented directly from the cell surface. The major source of inflammatory gluten is dietary gluten. Optimal reactivity of gliadin occurs when the protein is partially digested by small intestinal lysozyme and trypsin into proteolytic digests. These polypeptides of gluten can then make their way behind the epithelial layer of cells (membrane), where APCs and T-cells reside in the lamina propria. (See: Underlying conditions)
  The APC bearing DQ-gliadin peptide on the surface can bind to T-cells that have an antibody-like T-cell receptor the specifically recognized DQ2.5 with gliadin. The complex (APC-DQ-glaidin) thus stimulates the gliadin specific T-cells to divide. These cells cause B-cells that recognize gliadin to proliferate. The B-cells mature into plasma cells producing anti-gliadin antibodies. This does not cause coeliac disease and is an unknown factor in idiopathic disease. Enteropathy is believed to occur when tissue transglutaminase(tTG) covelantly links itself to gliadin peptides that enter the lamina propria of the intestinal villus. The resulting structure can be presented by APC (with the same gliadin recognizing DQ isoforms) to T-cells, and B-cells can produce anti-transglutaminase antibodies. This appears to result in the destruction of the villi. The release of gliadin by transglutaminase does not lessen disease. When tTG-gliadin undergoes hydrolysis (steals a water to cut the two apart), the result is deamidated gliadin. Deamidated gliadin peptides are more inflammatory relative to natural peptides. Deamidated gliadin is also found in foods that have added gluten, such as wheat bread, food pastes.
  The major gluten proteins that are involved in coeliac disease are the α-gliadin isoforms. Alpha gliadin is composed of repeated motifs that, when digested, can be presented by HLA-DQ molecules. DQ2.5 recognizes several motifs in gluten proteins, and therefore HLA-DQ can recognize many motifs on each gliadin (see Understanding DQ haplotypes and DQ isoforms on the right) However, numbers of different proteins from the grass tribe Triticeae have been found to carry motifs presented by HLA DQ2.5 and DQ8. Wheat has a large number of these proteins because its genome contains chromosomes derived from two goat grass species and a primitive wheat species.  The positions of these motifs in different species, strains and isoforms may vary because of insertions and deletions in sequence. There are a large number of wheat variants, and a large number of gliadins in each variant, and thus many potential sites. These proteins once identified and sequenced can be surveyed by sequence homology searches.
caption: Isoform pairings in DQ7.5/DQ2.2 result in 4 proteins isoforms, DQ2.5trans isoform is one(circled)
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